title: 6-(4-Pyridyl)pyrimidin-4(3H)-ones as CNS penetrant glycogen synthase kinase-3β inhibitors.
abstract: The discovery of a series of 6-(4-pyridyl)pyrimidin-4(3H)-ones derived from a hit compound with low molecular weight and sufficient chemical space is reported. Transformation of substituents led to subnanomolar potent inhibitors with in vivo tau phoshorylation lowering activity.
authors.affiliation: Research Division, Mitsubishi Tanabe Pharma Corporation, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Uehara
authors.forename: Aya
authors.initials: A
authors.lastname: Shoda
authors.forename: Keiichi
authors.initials: K
authors.lastname: Aritomo
authors.forename: Kenji
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Watanabe
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Ando
authors.forename: Masaki
authors.initials: M
authors.lastname: Shinoda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Ueno
authors.forename: Hideo
authors.initials: H
authors.lastname: Kubodera
authors.forename: Shinji
authors.initials: S
authors.lastname: Sunada
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Saito
authors.forename: Takahide
authors.initials: T
authors.lastname: Kaji
authors.forename: Shoichi
authors.initials: S
authors.lastname: Asano
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Eguchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yuki
authors.forename: Shinji
authors.initials: S
authors.lastname: Tanaka
authors.forename: Yukimi
authors.initials: Y
authors.lastname: Yoneyama
authors.forename: Takuro
authors.initials: T
authors.lastname: Niwa
mesh_terms: D001665:Binding Sites; D004789:Enzyme Activation; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D062105:Molecular Docking Simulation; D011485:Protein Binding / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D047428:Protein Kinase Inhibitors; D011744:Pyrimidinones; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3
keywords: Alzheimer’s disease; Glycogen synthase kinase 3β; Hyperphoshorylation; Pyrimidin-4(3H)-one; Tau protein